Our goal is to define the role played by the nerves of the endocrine pancreas in regulating insulin secretion. THe availability of an innervated, cross-perfused pancreas preparation permits us to examine the influence of the autonomic nerves without interference from confounding humoral stimuli. In separate experiments we shall infuse glucose, 3-O-methylglucose, epinephrine or insulin into a small dog whose innervated, in situ, pancreas is cross-perfused with blood from a large dog. Since the only functional connection between the body of the small dog and his pancreas will be autonomic nerves, infusions into him can cause changes in the insulin secretion rate only by way of these nerves. When a change is observed, experiments will be done to delineate the neural structures in the small dog responsible for the neuroendocrine response. Glucose and immunoreactive insulin concentrations will be determined in pancreatic effluent and pancreatic arterial plasma. Insulin secretion rates will be calculated. This work may result in a better understanding of the mechanisms responsible for disordered glucose metabolism in a number of human diseases.